On postnatal day 8, prairie vole pups were randomly assigned a treatment of 1mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), eticlopride (D2 antagonist), or saline vehicle. As adults, females treated with eticlopride exhibited reduced anxiety-like behavior in an elevated plus maze and a reduction in infanticidal behavior. These behavioral effects were not seen in males. These data demonstrate that a single exposure to a D2 antagonist during development can have persistent, sex-specific effects on behavior into adulthood.

Stress and anxiety play a role in many psychological processes including social behavior. The present study examines the effects of urocortin II (UCN II) on spontaneous parental behavior in adult prairie voles (Microtus ochrogaster). UCN II was found to increase passive parental behavior in voles while not affecting any stress-related measures. Delineating the mechanism of this change will aid in our understanding of the regulation of parenting.

Prairie voles (Microtus ochrogaster) are monogamous rodents that display high levels of affiliative behaviors, including pair-bonding, biparental care, and cooperative breeding. Species differences in basal cocaine- and amphetamine-regulated transcript (CART) mRNA and peptide expression have been found between prairie voles and polygamous meadow voles. Therefore, we hypothesized that the CART system may play a role in the regulation of social behavior in this species. Male and female adult prairie voles were placed in a cage either alone, or with a novel social partner of the same or opposite sex. After 45 min, subjects were sacrificed and CART peptide expression was examined using immunohistochemistry. We examined fifteen hypothalamic, limbic, and hindbrain regions of interest, focusing on areas that show species-specific patterns of expression. We found that subjects paired with a novel conspecific had lower levels of peptide in the bed nucleus of the stria terminalis (BNST) than isolated animals. This may reflect increased peptide release following increased dopaminergic activity in animals exposed to a novel conspecific. Additionally, CART peptide was higher in the nucleus accumbens (NAc) of subjects paired with an opposite sex partner compared to those paired with a same-sex conspecific, although there was no difference between isolated subjects and either socially housed group. These findings suggest that CART in the NAc is differentially responsive to the sex of adult conspecifics and that the social environment influences CART expression in the prairie vole in a region- and stimulus-specific manner.

The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques' (Macaca mulatta) friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center (CNPRC). Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay (EIA). Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject), multiplex friendships (friendships displayed in more than one behavioral domain), and total number of friendships. Females' number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males' plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual's psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in which it is administered.

The monogamous prairie vole displays developmental sensitivity to early pharmacological manipulation in a number of species-typical social behaviors. The long-term consequences of altering the neonatal dopamine system are not well characterized. This study examined whether early manipulation of the dopamine system, a known mediator of adult prairie vole social behavior, during neonatal development would affect adult aggressive and attachment behaviors. Eight-day-old pups were given a single treatment with either 1 mg/kg of SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), eticlopride (D2 antagonist), or saline vehicle. As adults, animals received tests for intrasexual aggression and partner preference. Activation of D1-like receptors in pups impaired partner preference formation, but had no effect on aggression. Other neonatal treatments had no effect on their behavior as adults. To determine whether D1 activation in pups induced changes in dopamine receptor expression, we performed autoradiography on striatal tissue from a second cohort of saline-treated and SKF38393-treated animals. Although sex differences were observed, we found no treatment differences in D1 or D2 receptor binding in any striatal subregion. This study shows that exposure to a single early pharmacological alteration of dopamine receptor activity may have long-term effects on the social behavior of prairie voles.

The steroid hormone cortisol has been associated with different levels of "stress" as well as different reproductive conditions in many primates. In callitrichids, cortisol has more often been reflective of female reproductive status than of chronic stress. In this study, we addressed the hypothesis that wild golden lion tamarin (Leontopithecus rosalia) females, whose social structure is characterized by low aggression and high social support, would not show rank ("stress")-related differences in glucocorticoids but would show reproductive changes. We collected 710 fecal samples from 22 adult females in Poço das Antas Reserve, Brazil, and nearby reintroduction areas, and assayed them for cortisol. Differences in cortisol levels were found between different reproductive conditions. Females in the first trimester of pregnancy had lower cortisol levels than nonpregnant females, although we did not differentiate between basal and ovulating levels in nonpregnant females. Cortisol rose in the third trimester of pregnancy. Primiparous females had a higher rise in the third trimester than multiparous females. No differences in cortisol levels were found among dominant females, ovulatory subordinate females, or anovulatory subordinate females. These results are similar to those obtained in other studies of callitrichid females. The lack of differences in cortisol excretion between dominants and subordinates is likely due to the low levels of overt aggression and the high level of social support available to subordinate females.

The direct costs of paternal care are relatively well documented in primates, however little research has explored these effects in monogamous rodents. The present study examines the long-term effects that pairing and parenting have on male prairie voles. We hypothesized that there would be a significant weight loss over the course of pairing and parenting, presumably from the energetic demands that accompany these changes in social condition. In a longitudinal study, we followed ten male prairie voles through being housed with their brother; paired with a female; and caring for three consecutive litters. We found a significant drop in bodyweight across time, with maximum weight loss near the weaning of the first litter. At that same time, feeding increased, leading to possible recovery in weight; however, leptin levels dropped precipitously across time and did not recover. Corticosterone did not change significantly across time points, and overall activity levels also did not vary significantly over the course of the study. In addition, newly paired males showed a significant increase in preference for a 2% sucrose solution during a three-hour test, indicating a metabolic need for more calories. A cross-sectional study confirmed leptin and corticosterone findings, and showed significant loss of subcutaneous (inguinal) fat in males that had cared for a litter of pups, when compared to males housed with their brothers or newly paired males. These results suggest that cohabitation with a female, and caring for pups, all have costs for male prairie voles.

There has been intensified interest in the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in autism spectrum disorders (ASD) given their role in affiliative and social behavior in animals, positive results of treatment studies using OT, and findings that genetic polymorphisms in the AVP-OT pathway are present in individuals with ASD. Nearly all such studies in humans have focused only on males. With this preliminary study, we provide basic and novel information on the involvement of OT and AVP in autism, with an investigation of blood plasma levels of these neuropeptides in 75 preadolescent and adolescent girls and boys ages 8-18: 40 with high-functioning ASD (19 girls, 21 boys) and 35 typically developing children (16 girls, 19 boys). We related neuropeptide levels to social, language, repetitive behavior, and internalizing symptom measures in these individuals. There were significant gender effects: Girls showed higher levels of OT, while boys had significantly higher levels of AVP. There were no significant effects of diagnosis on OT or AVP. Higher OT values were associated with greater anxiety in all girls, and with better pragmatic language in all boys and girls. AVP levels were positively associated with restricted and repetitive behaviors in girls with ASD but negatively (nonsignificantly) associated with these behaviors in boys with ASD. Our results challenge the prevailing view that plasma OT levels are lower in individuals with ASD, and suggest that there are distinct and sexually dimorphic mechanisms of action for OT and AVP underlying anxiety and repetitive behaviors. Autism Res 2013, 6: 91-102. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Pair bonding leads to increases in dopamine D1 receptor (D1R) binding in the nucleus accumbens of monogamous prairie voles. In the current study, we hypothesized that there is similar up-regulation of D1R in a monogamous primate, the titi monkey (Callicebus cupreus). Receptor binding of the D1R antagonist [¹¹ C]-SCH23390 was measured in male titi monkeys using PET scans before and after pairing with a female. We found that within-subject analyses of pairing show significant increases in D1R binding in the lateral septum, but not the nucleus accumbens, caudate, putamen, or ventral pallidum. The lateral septum is involved in a number of processes that may contribute to social behavior, including motivation, affect, reward, and reinforcement. This region also plays a role in pair bonding and paternal behavior in voles. Our observations of changes in D1R in the lateral septum, but not the nucleus accumbens, suggest that there may be broadly similar dopaminergic mechanisms underlying pair bonding across mammalian species, but that the specific changes to neural circuitry differ. This study is the first research to demonstrate neuroplasticity of the dopamine system following pair bonding in a non-human primate; however, substantial variability in the response to pairing suggests the utility of further research on the topic.